Is TOE1 p.Leu392= (c.1176G>A) pathogenic?

TOE1 p.Leu392= (c.1176G>A) is classified Benign/Likely benign in TOE1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-05-01). Rare (popmax 0.807%, nfe); Associated with pontocerebellar hypoplasia type 7.

What condition is associated with TOE1 p.Leu392= (c.1176G>A)?

TOE1 p.Leu392= (c.1176G>A) is associated with pontocerebellar hypoplasia type 7 (ClinVar).

How common is TOE1 p.Leu392= (c.1176G>A) in the general population?

TOE1 p.Leu392= (c.1176G>A) is rare (popmax 0.807%, nfe) (gnomAD).

TOE1 p.Leu392=

c.1176G>A · rs149142910 · VCV780001

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.807%, nfe)

Conditions

pontocerebellar hypoplasia type 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.86	GERP -0.2, phastCons 0.027
Overall
CADD	0.756	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.807% European (non-Finnish) · 9,526/1,180,014 alleles

Filtering AF 0.794% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.788%

Overall 0.76% 12,274/1,614,018 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.78%	36
Amishnot grpmax-eligible	2.2%	46
European (non-Finnish)grpmax	0.807%	124
Remaining individualsnot grpmax-eligible	0.79%	127
Admixed American	0.3%	333
Ashkenazi Jewishnot grpmax-eligible	0.287%	348
Middle Eastern	0.132%	758
African / African-American	0.119%	843
South Asian	0.103%	969

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TOE1
Protein: p.Leu392=
Coding: c.1176G>A
MANE Select: NM_001048174 · reported on NM_025077
dbSNP: rs149142910
Type: single nucleotide variant
Location: chr1:45343345 (GRCh38)

Full TOE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pontocerebellar hypoplasia type 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/toe1-p-leu392 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown